MU researchers get to the 'heart' of SMA therapy

COLUMBIA — New developments in Spinal Muscular Atrophy research at MU are pointing toward big changes in treatment.

Spinal Muscular Atrophy is a genetic disorder that affects between 2.5 and 3.3 percent of people, according to an MU news release. According to the Spinal Muscular Atrophy Foundation, people affected by the disorder are missing a gene that produces SMN-1, a protein necessary for healthy motor neurons. Motor neurons send the signal to muscles that make them move. When there is not enough SMN-1 in the body, the neurons die, leading to loss of mobility.

Christian Lorson is a professor of veterinary pathobiology and molecular microbiology and immunology at MU. Working with a team of scientists, he has found that the disorder affects the heart and neurons separately.

Research on animals has shown that, even as embryos, mice with Spinal Muscular Atrophy can show heart defects before neuron damage, said Monir Shababi, the research scientist heading the project. This discovery shook the foundation of the treatment knowledge base.

“[Clinicians] always thought the heart failure was a consequence of neurodegeneration, which is known as the major defect in SMA patients,” Shababi said of the heart defects.

This research would suggest that heart failure is a direct result of the disorder, rather than a link in the chain of events.

“If you have a genetic defect, it’s something that happened before conception,” said Jennifer Kussmann, a genetic counselor at MU. "So we can’t go back in time and rebuild the muscle.”

However, the knowledge of a heart defect in a person with Spinal Muscular Atrophy would allow clinicians to treat defects before they become life-threatening, Shababi said.

“As soon as the patient is diagnosed with SMA, [clinicians] will look at the heart and possibly give some medication to delay the heart failure,” Shababi said. “It just creates an awareness that something is going wrong with the heart.”

This awareness could encourage a change in treatment of the disorder.

“With new, SMA-specific therapeutics on the horizon, it will be important to address the entire disease, such as motor neurons and cardiac issues,” Lorson said.

People with Spinal Muscular Atrophy also have the option of replacing that missing gene — a process that has worked with animal models. However, researchers realize the experiments are not conclusive enough to guarantee success in humans.

“Models of disease are just that – they’re models and therefore only present part of the human condition,” Lorson said. When working with Spinal Muscular Atrophy in animals, “you’re doing a new experiment, you’re not verifying the animal results,” he said.

Replacing the SMN protein like a supplement is also an option, but it’s challenging because it requires crossing the blood-brain barrier, which is the body’s natural defense of the central nervous system, Lorson said.

Lorson and his team’s discovery is not a cure, but a step toward better treatment and better quality of life for people living with the disorder, he said.